Bottom Line:
PLGA/PLA polymeric nanoparticles could potentially enhance the effectiveness of convective delivery of drugs, such as carboplatin, to the brain, by enabling a more sustained dosage over a longer time than otherwise possible.For a core-coat nanoparticle formulation, the development of smaller nanopores, following an extended induction period with no structural change, was associated with the onset of substantial drug release.Hence, the specific reasons for the effectiveness of the synthesis route, for obtaining core-coat nanoparticles with delayed release, have been elucidated.

fig0035: NMR cryoporometry data (symbols) for bulk aCSF solution, and for polymer nanoparticles from batch D immersed in aCSF at different time periods, namely ∼2 h, ∼2 days and ∼9 days. The percentage carboplatin released has been plotted (line) against time on the secondary axes.

Mentions:
The melting curves of aCSF solution containing nanoparticles from batch D, and their drug release profile are plotted in Fig. 7. It was found that nanoparticles from batch D exhibited a spontaneous or burst release of ∼60% of its drug content within the first 12 h. After this initial burst release (within half a day), the remaining ∼40% of the drug was gradually released over ∼10.5 days. A declining release rate was noted in the drug release profile tail at later times, unlike the burst release samples seen earlier. The cryoporometry melting curves were obtained after ∼2 h, ∼2 days and ∼9 days of incubation. A roughly three times increase in the volume of small to medium sized (∼2–4 nm, corresponding to ∼248–260 K) pores was evident in the melting curves when comparing the results obtained following 2 h of incubation, and following ∼2 days of incubation. This time period corresponded to a significant jump in the amount of drug released from the nanoparticles (∼62% drug released). At later times, it was found that there was little change in the melting profile which corresponded to the lesser amount of drug released over that period (∼16% drug released).

fig0035: NMR cryoporometry data (symbols) for bulk aCSF solution, and for polymer nanoparticles from batch D immersed in aCSF at different time periods, namely ∼2 h, ∼2 days and ∼9 days. The percentage carboplatin released has been plotted (line) against time on the secondary axes.

Mentions:
The melting curves of aCSF solution containing nanoparticles from batch D, and their drug release profile are plotted in Fig. 7. It was found that nanoparticles from batch D exhibited a spontaneous or burst release of ∼60% of its drug content within the first 12 h. After this initial burst release (within half a day), the remaining ∼40% of the drug was gradually released over ∼10.5 days. A declining release rate was noted in the drug release profile tail at later times, unlike the burst release samples seen earlier. The cryoporometry melting curves were obtained after ∼2 h, ∼2 days and ∼9 days of incubation. A roughly three times increase in the volume of small to medium sized (∼2–4 nm, corresponding to ∼248–260 K) pores was evident in the melting curves when comparing the results obtained following 2 h of incubation, and following ∼2 days of incubation. This time period corresponded to a significant jump in the amount of drug released from the nanoparticles (∼62% drug released). At later times, it was found that there was little change in the melting profile which corresponded to the lesser amount of drug released over that period (∼16% drug released).

Bottom Line:
PLGA/PLA polymeric nanoparticles could potentially enhance the effectiveness of convective delivery of drugs, such as carboplatin, to the brain, by enabling a more sustained dosage over a longer time than otherwise possible.For a core-coat nanoparticle formulation, the development of smaller nanopores, following an extended induction period with no structural change, was associated with the onset of substantial drug release.Hence, the specific reasons for the effectiveness of the synthesis route, for obtaining core-coat nanoparticles with delayed release, have been elucidated.